Anesthetic Management of the Child with an Anterior Mediastinal Mass
Mediastinal masses may arise from structures normally located in the mediastinum, from those that pass through the mediastinum during development, or from metastatic disease that arises from tumors elsewhere in the body. In children, mediastinal masses tend to be more prevalent in males than in females. , The majority are caused by lymphomas, followed by bronchial cysts, teratomas, vascular malformations, and neurogenic tumors.
Mediastinal masses may present with nonspecific respiratory or cardiovascular symptoms, such as coughing, or present with more severe symptoms, such as superior vena cava syndrome, pulmonary artery obstruction, or culminate in superior mediastinal syndrome (airway compression/tracheal obstruction, vascular compression).
The presence of an anterior mediastinal mass should be regarded as a clinical emergency. Early diagnosis and management are crucial for providing the best chance for a favorable outcome. The latter undoubtedly adds to the challenge of the anesthetic management of these patients, since symptoms such as respiratory or cardiovascular compromise may not be optimized before anesthesia.
General anesthesia confers considerable risk, since the effects of mediastinal masses on airway and vascular structures can impede gas exchange or reduce cardiac output. The symptoms at presentation are essential to developing an anesthetic plan and have been shown to be predictive of anesthetic-related morbidity. In a retrospective review of 118 pediatric patients who presented with mediastinal masses, four preoperative features were significantly associated with anesthetic complications: main‐stem bronchus compression, great vessel compression, orthopnea, and upper body edema. The presence of pleural or pericardial effusions, ventricular dysfunction, tracheal compression (cross-sectional area <50%), and stridor are also associated with anesthetic related morbidity.
Anesthetic Management
The anesthetic management begins with a careful review of the child’s history, symptoms, clinical signs, and radiographic images (computed tomography and/or chest x-ray). In general, patients without orthopnea or cardiovascular symptoms and minimal radiographic evidence of airway obstruction may likely be anesthetized safely. However, physical signs and radiographic evidence have not been consistently shown to be predictive of potential complications; therefore general anesthesia or deep sedation should be avoided whenever possible, and when required, it is essential that the anesthesiologist establishes communication with the surgeon, has a set plan for sedation or anesthesia, and has a plan for rescue in the event of cardiopulmonary compromise. These include repositioning the patient (lateral or prone), the ability to perform rigid bronchoscopy to relieve tracheal compression, and the ability to perform a sternotomy and provide cardiopulmonary bypass or extracorporeal membrane oxygenation (ECMO).
Patients with signs of orthopnea, stridor, dyspnea at rest, and/or a >70% reduction in tracheal cross-sectional area are deemed high-risk, and general anesthesia should be avoided unless absolutely necessary. In older children, tissue diagnosis under local anesthesia has been associated with lower risk of anesthetic complications and has been successfully accomplished in several series. , Distraction techniques such as counting, listening to music, and nonprocedure-related talk have been shown to be effective. However, younger children and those undergoing surgical resection of large mediastinal masses may require a general anesthetic. In this instance, an anesthetic plan that ensures spontaneous respiration is generally preferable. Spontaneous ventilation typically preserves the patency of the intrathoracic airways. On the other hand, positive pressure ventilation may worsen airway compression (e.g., through neuromuscular blockade and/or deep anesthesia reducing support of the surrounding tracheobronchial musculature) and also reduce cardiac output by reducing venous return.
The airway may be managed by mask ventilation only, with a laryngeal mask airway, or with endotracheal intubation. Several methods have been described for the maintenance of anesthesia, including a mixture of sevoflurane in oxygen and halothane in heliox, and low-dose infusions of propofol, dexmedetomidine, and ketamine. The ability of dexmedetomidine and ketamine to provide sedation with minimal respiratory depression has proven beneficial in anesthetizing children with anterior mediastinal masses.
It is noteworthy that several authors have reported cases where intubation has been successfully performed in children with mediastinal masses. , In the event that an endotracheal intubation is necessary, advancement of the endotracheal tube past the segment of obstruction, typically through external compression, may have to be performed. Regardless of the choice of airway management, neuromuscular blockade is generally not recommended because the relaxation of supporting tracheobronchial musculature may contribute to further worsening of airway compromise. However, if neuromuscular blockade is deemed necessary, it is imperative to establish the ability to adequately ventilate the patient before administering muscle relaxants.
Summary
The management of the child with an anterior mediastinal mass poses a significant challenge to anesthesiologists. Potential respiratory and cardiovascular complications may be exacerbated under anesthesia, and plans to manage potential complications should be communicated to the entire team before initiation of care. Where possible, diagnostic procedures are best performed with local anesthesia with minimal-to-no sedation. Where deep sedation or general anesthesia is required, maintenance of spontaneous ventilation with or without an endotracheal tube is preferable. Neuromuscular blockade should be avoided whenever possible.
Anesthesia for Pediatric Radiotherapy
Unlike adults and older children, most children under 2 years of age require anesthesia or sedation for the successful completion of a course of radiotherapy treatments. This is mainly because complete immobilization, which is required for safe and effective radiotherapy, cannot be reliably accomplished in very young children without sedation or anesthesia.
This, in and of itself, presents several challenges. Perhaps most concerning is the fact that younger children may have to be exposed to multiple anesthetics over a relatively short period of time. The inherent risks associated with anesthetizing a very young child and the exposure to the side effects of anesthetic agents used are therefore amplified. In this regard, the safety profile of the chosen anesthetic technique gains further significance. Furthermore, to ensure that there is no interference with the radiotherapy plan from changes in airway management or patient positioning, it is important that the chosen method of anesthesia remains unchanged over the period of treatment and that it is easily replicable. Other challenges include choosing an anesthetic that may facilitate rapid awakening and rapid discharge, since most radiotherapy facilities treat multiple patients or may not have a designated postoperative recovery area.
Airway Management
Several studies have demonstrated that anesthesia in children undergoing radiation therapy may be safely performed by spontaneous ventilation and an unprotected airway. In a large series of 340 children who had undergone 9328 radiotherapy procedures under anesthesia, supplemental oxygen was provided with a face mask or nasal cannula. In another large series describing the anesthetic management of 177 children who had undergone 3833 radiotherapy procedures, supplemental oxygen was provided by face mask in both the supine and prone positions. The placement of an oral airway or laryngeal mask airway was required in rare cases.
General Anesthesia versus Conscious Sedation
In a meta-analysis of anesthesia complications of pediatric radiation therapy, general anesthesia was shown to be superior to conscious sedation with regard to maintaining satisfactory procedural sedation while maintaining low respiratory and cardiovascular complication rates.
Medications
Several medications and anesthetic agents have been used for the successful completion of daily recurrent anesthesia. These include intravenous propofol, inhalational volatile anesthetics, ketamine, , midazolam, chloral hydrate, and dexmedetomidine. ,
Propofol
The rapid onset and quick recovery from propofol has made it the anesthetic of choice in several centers where daily recurrent anesthesia is performed. , In a retrospective study of 3833 pediatric radiotherapy/simulation procedures performed under propofol-based total intravenous anesthesia, Anghelescu et al. reported a very low rate of complications (1.3%). In this study, the authors described their technique of administering 1 mg/kg boluses of propofol until loss of consciousness, followed by 100–250 µg/kg/min (6–15 mg/kg/h). Additional boluses of 1 mg/kg were administered if the child responded to stimulation. Furthermore, in a survey of anesthesia practices at proton radiotherapy centers worldwide, propofol was the maintenance anesthetic of choice in the majority of centers. The reduction of recovery time by propofol has been consistently observed when propofol is used as a sole agent in children undergoing procedural sedation. The mean weighted difference in recovery time reduction has been estimated to be approximately 10 min.
Volatile Anesthetics
The slower onset and recovery from volatile anesthetics pose a significant challenge during their use for multiple repeated anesthetics. That said, several institutions safely administer volatile anesthetics for daily repeated procedures. For example, in the aforementioned survey of anesthesia practices for proton radiotherapy, 36% of the respondents indicated that they used volatile anesthesia with a laryngeal mask airway. This may be because treatment sessions during proton radiotherapy could be considerably longer than conventional radiotherapy, making differences in recovery times between volatile anesthetics and propofol less significant. Another factor may be the need to transport patients to recovery rooms that are located at a considerable distance from the treatment location, making rapid recovery less desirable.
Dexmedetomidine
Dexmedetomidine is a selective alpha-2-adrenoceptor agonist with anxiolytic and analgesic properties, and minimal respiratory depressant effects. The latter property makes it attractive as a sedative in remote settings where help from additional personnel may be difficult to obtain. In their description of two case reports, Kim et al. used dexmedetomidine to provide sedation for over 20 sessions of radiotherapy in two young children. The authors administered a loading dose of 1.5–2.0 µg/kg of intravenous dexmedetomidine over 10 min, followed by a maintenance dose of 0.5–2 µg/kg/h. An increase in dexmedetomidine requirements was observed with subsequent treatment sessions. In another publication, Shukry et al. described the use of dexmedetomidine as the primary sedative agent in a 21-month-old child undergoing brain radiotherapy. In this case report, the authors administered a loading dose of 1 µg/kg over 10 min, followed by an infusion at 10 µg/kg/h. A heart rate lower than 90 beats/min was treated with 10–20 µg/kg of atropine.
Ketamine
Ketamine is a dissociative agent with excellent amnestic and analgesic properties. However, its side effects, including increased secretions, involuntary movements, hallucinations, nightmares, and a slow recovery profile, make it less desirable as an agent for daily repeated anesthesia. In a meta-analysis of anesthesia complications of pediatric radiation therapy, the complication rates associated with the use of ketamine were as high as 24%. However, some authors have described its use in pediatric patients undergoing daily radiotherapy sessions. , In a single-blind prospective study, Sanusi et al. described the safe intravenous administration of a combination of ketamine (2 mg/kg) and atropine (10 µg/kg) to 33 children who were undergoing daily radiotherapy treatments. In that study, the investigators observed a progressive decrease in recovery times from a mean of 13.7 min at initiation of treatment to a mean of 7.7 min at the last treatment. In another publication, Soyannwo et al. described the safe repeated intramuscular administration of ketamine at a dose of 5–13 mg/kg on 280 occasions to 15 children. In that study, involuntary movements were observed in more than half of the study population but resulted in interruption of treatment in only 2% of patients. Time to complete recovery varied and ranged from 15 to 90 min.
Midazolam
Midazolam has been used in combination with ketamine for the successful completion of radiotherapy in children. This combination of drugs takes advantage of the anxiolytic properties of midazolam and the dissociative anesthesia offered by ketamine. Furthermore, the minimal respiratory depressant effects of lower doses of each of these drugs may be advantageous. In a retrospective study, describing the use of midazolam and ketamine for sedation for diagnostic and therapeutic procedures in children, Parker et al. described the intravenous administration of 0.05–0.1 mg/kg midazolam, followed by a 0.5–1 mg/kg dose of ketamine. Additional doses of ketamine 0.5–1 mg/kg were administered during lengthy procedures. In that study, two patients experienced emergence agitation. Another two patients were reported to have sleep disturbances (nightmares). However, both of these patients received ketamine with subsequent procedures at a reduced dose without a repetition of the sleep disturbances. The incidence of vomiting was relatively high (2.9%), and recovery times ranged from 15 to 120 min. Compared to propofol, the use of midazolam for repeated sedations in children undergoing radiotherapy has been associated with lower odds of a successful outcome.
Chloral Hydrate
The use of chloral hydrate for procedural sedation has been associated with a significant risk of complications and treatment failure. In a prospective observational study of repeated sedations for the radiotherapy in children with cancer, the use of chloral hydrate was associated with a 23% incidence rate of complications. Furthermore, treatment was considered unsatisfactory in 40% of the patients, and in another 20%, treatment could not be initiated. As a result of these findings, the authors concluded that chloral hydrate was not the most suitable drug for children undergoing radiotherapy under anesthesia.
Complications
Complication rates in children undergoing repetitive anesthesia for radiotherapy are generally low. In a series of 177 children who had undergone 3833 radiotherapy procedures under anesthesia, Anghelescu et al. reported an overall complication rate of 1.3%. In their study, procedure duration; total propofol dose; the use of use of adjuncts, such as opioids, benzodiazepines, and barbiturates, in addition to propofol; and anesthesia for simulation (vs. radiotherapy) were associated with an increased risk of complications. In another retrospective study of 130 children who had undergone 1376 radiation treatment sessions under anesthesia, Yildirim et al. reported an overall complication rate of 2.6%. Similar to the findings of Anghelescu et al., the total propofol dose was associated with a risk of complications. However, unlike the study by Anghelescu et al., the use of adjuncts in addition to propofol was associated with a lower complication rate. This difference may be explained by the type of adjuncts used. Unlike the study by Yildirim et al. where ketamine and midazolam were used as adjuncts, opioids were used in the study by Anghelescu et al. and may have accounted for a higher rate of complications.
In a meta-analysis of anesthesia complications of pediatric radiation therapy, the most common complications were respiratory in nature (e.g., airway obstruction, broncho/laryngospasm, desaturation, apnea), followed by those that were cardiovascular in nature (e.g., tachycardia, bradycardia, arrhythmias, hypotension) and nausea/vomiting. Other complications included those associated with vascular access devices, such as infection, breakage, or extravasation, which was observed in up to 25% of patients. Thus attention to sterility during daily access of venous devices is essential.
Neurotoxicity of Anesthetic Agents
Concerns regarding the possible neurotoxic effects of repetitive anesthesia continue to be raised by parents. To date there have been no studies examining the neurotoxic effects of repetitive anesthesia in children undergoing radiotherapy. However, in a recent cohort study of 212 survivors of childhood acute lymphoblastic leukemia who underwent 5699 exposures to general anesthesia, higher cumulative doses of anesthetics and longer anesthesia duration significantly contributed to neurocognitive impairment and neuroimaging abnormalities observed at a median of 7.52 years after diagnosis. This timeframe was well beyond the expected neurotoxic effects of chemotherapy. The confounding neurotoxic effects of cranial irradiation make this challenging to study in children undergoing radiotherapy.
By contrast, Oba and Türk presented the case of a 9-year-old child who received 80 separate anesthetics over a period of 6 years in order to facilitate treatment for corrosive esophagitis. The anesthetic agents used included propofol, fentanyl, rocuronium, and sevoflurane. After the last anesthetic, cognitive function was measured using the Wechsler Intelligence Scale for Children-Revised. A total score of 97 (corresponding to normal intelligence) was obtained. The Child Behavior Checklist was completed by his mother. The questionnaire detected no abnormalities except for minor attention problems. In this particular case, there were no permanent adverse effects due to multiple anesthesia. However, studies investigating the potential neurotoxic effects of repetitive anesthesia in children undergoing radiotherapy are warranted.
Summary
The anesthetic management of children undergoing repetitive anesthesia for radiotherapy presents unique challenges. The ability to replicate the anesthetic management with minimal to no interruption of the radiation plan is essential. To date, continuous propofol infusions with supplemental oxygen delivered by face mask or nasal cannula is preferred by most centers. There is still a lack of studies investigating the neurotoxic effects of repetitive anesthesia in children undergoing radiotherapy.
Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an extensive surgical procedure that offers a chance for cure, or more frequently, palliative control of peritoneal spread of malignancies. In children, this procedure can be performed in patients with peritoneal spread of tumors, such as desmoplastic round cell tumor, rhabdomyosarcoma, mesothelioma, and colorectal cancer. Complete cytoreduction is critical to achieving prolonged survival in this group of patients. The procedure may involve the removal of several hundred tumor nodules; thus aggressive cytoreduction is typically performed, with procedures typically lasting up to 12 h and blood loss estimates of up to 175 mL/kg. This is then followed by the instillation of heated (40.5°C–41.0°C) chemotherapy (e.g., cisplatin) into the peritoneal cavity for up to 90 min.
Appropriate anesthetic management is essential for the success of this procedure. A preanesthetic evaluation is usually performed 1 to 2 weeks before the procedure. During this visit, aspects of care, including the possible preoperative transfusion of blood and blood products, and pain management options (epidural analgesia vs. patient controlled analgesia) are discussed. It is notable that children presenting for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy may be anemic or coagulopathic from extensive disease or the side effects of neoadjuvant chemotherapy, thus necessitating possible correction of those factors before surgery. For the most part, children are admitted the day before surgery for preoperative hydration and mechanical bowel preparation. This presents an opportunity for correction of any hematologic or electrolyte abnormalities before surgery.
A general anesthetic with volatile agents, opioids, and epidural analgesia is typically performed. There has also been some limited experience with total intravenous anesthesia. Adequate large bore venous access must be ensured and an arterial line is necessary. Although central lines are not always required during the intraoperative period, they are often used for the correction of potassium and calcium in the postoperative period or for hemodynamic support, for example, norepinephrine infusion.
Intraoperative analgesia typically consists of a combination of epidural analgesia (e.g., bupivacaine 0.075% with hydromorphone 2–5 µg/mL) and a balanced general anesthesia with a continuous infusion of opioids (fentanyl or sufentanil) and supplemental intravenous acetaminophen. Intraoperative opioid administration of up to 5.8 morphine equivalents per kilogram has been reported. In general, total intravenous anesthesia with propofol, dexmedetomidine, and ketamine in combination with epidural analgesia has resulted in lower intraoperative opioid administration. However, this reduced opioid administration has not been associated with lower postoperative opioid consumption.
The nephrotoxic side effects of some of the intraperitoneal chemotherapeutic agents, for example cisplatin, make fluid management a critical component of the anesthetic management. In addition to preoperative hydration with crystalloid infusions at 1.5 times the maintenance rate, intraoperative fluids are given to maintain a urine output ≥2 mL/kg/h. Respective intraoperative crystalloid and colloid transfusions of up to 208 mL/kg and 104 mL/kg have been reported.
Packed red blood cells are transfused to maintain a hemoglobin value ≥100 mg/L (>10 g/dL), and blood products are transfused to keep values within normal limits. Red blood cell transfusion rates of up to 80% with an average transfusion volume of 39 mL/kg were reported by one retrospective study. Children with either a lower preoperative hemoglobin value, lower body mass index, or higher American Society of Anesthesiologists physical status score were more likely to receive blood transfusions.
In the absence of any contraindications, the majority of children may be extubated in the operating room and transferred to the intensive care unit for further postoperative monitoring.
ConclusionCRS-HIPEC in children is an extensive surgical procedure that requires careful attention to fluid management and may necessitate the transfusion of blood and blood products and hemodynamic lability in the postoperative period. Collaboration between the surgical, anesthesia, and critical care management teams is essential for the successful perioperative management of children undergoing this procedure.
References
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